Impact of NPSR1 gene variation on the neural correlates of phasic and sustained fear in spider phobia-an imaging genetics and independent replication approach.

Elisabeth J Leehr, Leonie S Brede, Joscha Böhnlein, Kati Roesmann, Bettina Gathmann, Martin J Herrmann, Markus Junghöfer, Hanna Schwarzmeier, Fabian R Seeger, Niklas Siminski, Thomas Straube, Anna Luisa Klahn, Heike Weber, Miriam A Schiele, Katharina Domschke, Ulrike Lueken, Udo Dannlowski
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Abstract

The functional neuropeptide S receptor 1 (NPSR1) gene A/T variant (rs324981) is associated with fear processing. We investigated the impact of NPSR1 genotype on fear processing and on symptom reduction following treatment in individuals with spider phobia. A replication approach was applied [discovery sample: Münster (MS) nMS = 104; replication sample Würzburg (WZ) nWZ = 81]. Participants were genotyped for NPSR1 rs324981 [T-allele carriers (risk) versus AA homozygotes (no-risk)]. A sustained and phasic fear paradigm was applied during functional magnetic resonance imaging. A one-session virtual reality exposure treatment was conducted. Change of symptom severity from pre to post treatment and within session fear reduction were assessed. T-allele carriers in the discovery sample displayed lower anterior cingulate cortex (ACC) activation compared to AA homozygotes independent of condition. For sustained fear, this effect was replicated within a small cluster and medium effect size. No association with symptom reduction was found. Within-session fear reduction was negatively associated with ACC activation in T-allele carriers in the discovery sample. NPSR1 rs324981 genotype might be associated with fear processing in the ACC in spider phobia. Interpretation as potential risk-increasing function of the NPSR1 rs324981 T-allele via impaired top-down control of limbic structures remains speculative. Potential association with symptom reduction warrants further research.

NPSR1基因变异对蜘蛛恐惧症中阶段性和持续性恐惧的神经相关性的影响--一种成像遗传学和独立复制方法。
功能性神经肽 S 受体 1(NPSR1)基因 A/T 变异(rs324981)与恐惧处理有关。我们研究了 NPSR1 基因型对蜘蛛恐惧症患者恐惧处理和治疗后症状减轻的影响。我们采用了一种复制方法(发现样本:明斯特(MS)nMS=104;维尔茨堡(WZ)nWZ=81)。对参与者进行了 NPSR1 rs324981 基因分型(T-等位基因携带者[风险]与 AA 同源物[无风险])。在功能磁共振成像过程中采用了持续和阶段性恐惧范式。进行了一个疗程的虚拟现实暴露治疗(VRET)。评估了从治疗前到治疗后症状严重程度的变化以及疗程内恐惧感的减轻情况。发现样本中的 T 基因等位基因携带者与 AA 基因同卵双生者相比,前扣带回皮层(ACC)的激活程度较低,不受条件影响。在持续恐惧中,这种效应在一个中等效应大小的小群中得到了复制。没有发现与症状减轻有关。在发现样本中,T-等位基因携带者的会话内恐惧减少与 ACC 激活呈负相关。NPSR1 rs324981基因型可能与蜘蛛恐惧症患者ACC的恐惧处理有关。至于 NPSR1 rs324981 T-等位基因通过削弱边缘结构的自上而下控制而增加潜在风险的功能,目前仍是一种推测。与症状减轻的潜在联系值得进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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